WSO December 2023 – Issue 3 - 1163

Ademola et al.
1163
Reporting Items for Systematic Reviews and MetaAnalyses
(PRISMA) guidelines.24 The review protocol was
prospectively registered at PROSPERO (registration number:
CRD42020223133). The review was conducted using
the Studies, Data, Methods, and Outcomes (SDMO) framework.25
The study design (S) focused on RCTs, and the data
(D) were primary stroke trial results published in any biomedical
journal. The method (M) contrasts the prespecified
analyses in protocol to those in the published results, and
the outcome (O) was the reporting quality subgroup analysis
in stroke clinical trials. The three medical subject headings
(MeSH) used were RCTs, stroke trials, and subgroup
analysis/effect modifications (Tables S1-S4: Supplementary
Materials).
Eligibility criteria and search strategy
Eligible studies are included in this review if they (1)
reported at least one subgroup analysis along with the primary
outcome findings in the main publication, (2) had published
corresponding study protocols, and (3) were RCTs.
Non-human trials, systematic reviews, literature reviews,
meta-analyses, gray literature, conference abstracts, and
publications in languages other than English were excluded.
Studies whose protocols were not published or made available
elsewhere were also excluded. Four electronic medical
databases were searched for relevant publications from
inception until 24 March 2021, namely, (1) Medline/
PubMed, (2) Embase, (c) the Cochrane Central Register of
Controlled Trials (CENTRAL), and (3) Web of Science. The
identified studies were imported into Covidence, a webbased
application for conducting systematic reviews.26
Covidence eliminated duplicate studies and provided independent
reviewers with a customized review template.
Selection of studies and data extraction
Three reviewers (A.A., J.A., and A.O.) independently
screened titles and abstracts in duplicate to identify articles
that met the inclusion criteria. These reviewers completed the
full-text review of each eligible study and retrieved the necessary
data. Disagreements among reviewers were resolved via
a consensus process involving T.S. and B.K.M. Data extracted
from each included study were the first author's name and
country, year of publication, trial sample size, type of intervention,
the prespecified subgroup analysis in the original
protocol, and the number of subgroups analyzed in the primary
publication. Other data extracted were the subgroup
effect studied, the predicted direction of the effect modification,
whether the authors justified the subgroup effect, and
whether they used an appropriate statistical test.
Assessment of subgroup analyses' credibility
and risk of bias
The reviewers independently graded the credibility of each
reported subgroup effect in duplicate using ICEMAN
Data analysis
After rating the effects with the ICEMAN, a descriptive
analysis of the eligible subgroup effects was performed.
These analyses were stratified by the type of stroke trial
(acute stroke, primary, and prevention), sample size, and
credibility. Trend analysis was performed on the extracted
meta-data using three time periods: publications before
2010, between 2010 and 2014, and publications after 2014.
The time intervals were selected to account for scientific
progress in stroke trials. The revised CONSORT statement
was published in 2010, and 2015 was recognized as the year
of endovascular treatment due to many landmark stroke trials.12,28
Furthermore, the descriptive analysis of the risk of
bias based on the five domains of the RoB-2 was provided.
All analyses were conducted in R 4.2.0 and Stata 17.0.29,30
Results
A total of 9234 studies were imported into Covidence from
the four electronic databases, with 2889 duplicates removed
and 6345 articles screened. The reviewers eliminated 5798
publications as irrelevant at the title and abstract screening
stage. After excluding 473 studies at the full-text review
stage, 74 publications met the inclusion criteria (Table S6).
There was substantial agreement among the reviewers at
the title and abstract screening, with an interrater agreement
κ = 0.69. See the PRISMA workflow diagram in
Figure 1. Also, the PRISMA checklist is shown in Table S7.
Characteristics of included studies
Table 1 describes the characteristics of the included studies.
The 74 studies included in the review had a total sample
size of 249,305 trial participants and 647 subgroup effects,
with a median study sample size of 1264 (IQR: 380-3876).
There were 42 (57%) acute stroke trials and 73 (99%) were
multicenter trials. Twenty-five studies (34%) used the modified
Rankin scale as the primary outcome measure, while
International Journal of Stroke, 18(10)
criteria. The ICEMAN questions (and answers) with the
overall ratings are listed (Table S5 and Figure S1). Each
subgroup effect was assigned a credibility rating ranging
from " Very Low " to " High " based on the responses to the
questions. A subgroup effect was assigned a " Very low "
credibility rating if all the responses were " definitely no " or
" probably no, " and a " Low credibility " rating if there were
at least two " definitely no " responses. Furthermore, a subgroup
effect was given a moderate credibility rating when
there was only one " definitely no " or two " probably no "
responses, and a high credibility rating when none of the
responses were " definitely no " or " probably no. " Finally,
the reviewers used the Cochrane Risk-of-Bias tool for randomized
trials version 2 (RoB-2) to critically assess the risk
of bias in duplicate for each study.27
WSO December 2023 – Issue 3

Table of Contents for the Digital Edition of WSO December 2023 – Issue 3
